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https://www.readbyqxmd.com/read/28433656/impaired-endothelium-derived-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-isolated-from-female-otsuka-long-evans-tokushima-fatty-rats
#1
Takayuki Matsumoto, Shota Kobayashi, Makoto Ando, Shun Watanabe, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28414187/metatropic-dysplasia-in-third-trimester-of-pregnancy-and-a-novel-causative-variant-in-the-trpv4-gene
#2
Sara Bargiacchi, Matteo Della Monica, Roberto Biagiotti, Elena Andreucci, Serena Ciabattoni, Paolo Poggi, Marco Di Maurizio, Claudio Defilippi, Ettore Cariati, Sabrina Giglio
Prenatal diagnosis of skeletal dysplasias is particularly difficult for many reasons and differentiating these disorders in the prenatal period can be challenging because they are rare and many of the ultrasound findings are not necessarily pathognomonic for a specific disorder. The diagnosis is often made just after birth or exitus. The prenatal diagnosis of osteochondrodysplasias is based predominantly upon fetal ultrasound findings and it focuses substantially on the possible lethality of the disorder, without always being able to find a specific name for the disorder...
April 13, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28411253/a-new-path-to-platelet-production-through-matrix-sensing
#3
Vittorio Abbonante, Christian Andrea Di Buduo, Cristian Gruppi, Carmelo De Maria, Elise Spedden, Aurora De Acutis, Cristian Staii, Mario Raspanti, Giovanni Vozzi, David Kaplan, Francesco Moccia, Katya Ravid, Alessandra Balduini
Megakaryocytes in the bone marrow are immersed in a network of extracellular matrix (ECM) components that regulate platelet release into the circulation. Combining biological and bioengineering approaches, we found that the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechano-sensitive ion channel, is induced upon megakaryocyte adhesion on softer matrices. This response promoted platelet production by triggering a cascade of events that lead to calcium influx, β1 integrin activation and internalization, and Akt phosphorylation, responses not found on stiffer matrices...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28389775/erratum-to-sensitisation-of-trpv4-by-par2-is-independent-of-intracellular-calcium-signalling-and-can-be-mediated-by-the-biased-agonist-neutrophil-elastase
#4
Silvia Sostegni, Alexei Diakov, Peter McIntyre, Nigel Bunnett, Christoph Korbmacher, Silke Haerteis
No abstract text is available yet for this article.
April 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#5
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28381109/-express-prostanoid-dependent-spontaneous-pain-and-par2-dependent-mechanical-allodynia-following-oral-mucosal-trauma-involvement-of-trpv1-trpa1-and-trpv4
#6
Misa Ito, Kentaro Ono, Suzuro Hitomi, Tomotaka Nodai, Teppei Sago, Kiichiro Yamaguchi, Nozomu Harano, Kaori Gunnjigake, Ryuji Hosokawa, Tatsuo Kawamoto, Kiyotoshi Inenaga
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28372987/disrupting-sensitization-of-trpv4
#7
Konrad Mack, Michael J M Fischer
TRPV4 ion channels have a broad expression profile and were shown to contribute to enhanced pain sensation in inflammation. Directly blocking TRPV4 might run the risk of interfering with normal physiology, and has prompted to explore the interaction with the scaffolding protein AKAP79, an approach successfully used for TRPV1 channels. HEK293t cells express AKAP79, additional transfection did not sensitize human TRPV4. Application of trypsin facilitated responses to TRPV4 agonist GSK1016790A. Using a specific protease-activated receptor 2 agonist, involvement of an A-kinase anchoring protein in TRPV4 activation was demonstrated by inhibition with AKAP inhibitor peptide Ht31...
April 1, 2017: Neuroscience
https://www.readbyqxmd.com/read/28368307/trpv4-stimulation-induced-melatonin-secretion-by-increasing-arylalkymine-n-acetyltransferase-aanat-protein-level
#8
Hanan Awad Alkozi, Maria J Perez de Lara, Juan Sánchez-Naves, Jesús Pintor
Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymine N-acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied...
April 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28359774/trpv4-regulates-insulin-mrna-expression-and-ins-1e-cell-death-via-erk1-2-and-no-dependent-mechanisms
#9
M Billert, M Skrzypski, M Sassek, D Szczepankiewicz, T Wojciechowicz, S Mergler, M Z Strowski, K W Nowak
TRPV4 is a Ca(2+)-permeable, nonselective cation channel. Recently, TRPV4 was implicated in controlling peripheral insulin sensitivity, insulin secretion and apoptosis of pancreatic beta cells. Here, we characterize the role and potential mechanisms of TRPV4 in regulating insulin mRNA expression and cell death in insulin producing INS-1E cells and rat pancreatic islets. TRPV4 protein production was downregulated by siRNA. Intracellular calcium level was measured using Fluo-3 AM. Gene expression was studied by real-time PCR...
March 27, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28347703/afidopyropen-new-and-potent-modulator-of-insect-transient-receptor-potential-channels
#10
Ramani Kandasamy, Damian London, Lynn Stam, Wolfgang von Deyn, Xilong Zhao, Vincent L Salgado, Alexandre Nesterov
The commercial insecticides pymetrozine and pyrifluquinazon control plant-sucking pests by disturbing their coordination and ability to feed. We have previously shown that these compounds act by overstimulating and eventually silencing vanilloid-type transient receptor potential (TRPV) channels, which consist of two proteins, Nanchung and Inactive, that are co-expressed exclusively in insect chordotonal stretch receptor neurons. Here we show that a new insecticidal compound, afidopyropen, modulates chordotonal organs of American grasshoppers (Schistocerca americana) in the same fashion...
March 24, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28340683/trpv4-moves-toward-center-fold-in%C3%A2-rosacea-pathogenesis
#11
Yong Chen, Carlene D Moore, Jennifer Y Zhang, Russell P Hall, Amanda S MacLeod, Wolfgang Liedtke
Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 a translational-medical target in rosacea. However, signaling mechanisms causing increased expression of TRPV4 await elucidation. Moreover, we ask whether TRPV4-mediated Ca(++)-influx evokes mast cell degranulation.
April 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#12
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28303089/protease-activated-receptor-2-par2-induces-long-term-depression-in-the-hippocampus-through-transient-receptor-potential-vanilloid-4-trpv4
#13
Efrat Shavit-Stein, Avital Artan-Furman, Ekaterina Feingold, Marina Ben Shimon, Zeev Itzekson-Hayosh, Joab Chapman, Andreas Vlachos, Nicola Maggio
Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of N-methyl-D-aspartate receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28295351/when-size-matters-transient-receptor-potential-vanilloid-4-channel-as-a-volume-sensor-rather-than-an-osmo-sensor
#14
Trine L Toft-Bertelsen, David Krízaj, Nanna MacAulay
Transient receptor potential channel 4 of the vanilloid subfamily (TRPV4) is activated by a diverse range of molecular cues, such as heat, lipid metabolites, synthetic agonists, in addition to hyposmotic challenges. As a non-selective cation channel permeable to Ca(2+) , it transduces physical stress in the form of osmotic cell swelling into intracellular Ca(2+) -dependent signaling events. Its contribution to cell volume regulation might include interactions with aquaporin (AQP) water channel isoforms, although the proposed requirement for a TRPV4-AQP4 macromolecular complex remains to be resolved...
March 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28284871/pharmacological-evaluation-of-novel-6-aminopyridin-3-yl-4-pyridin-2-yl-piperazin-1-yl-methanone-derivatives-as-trpv4-antagonists-for-the-treatment-of-pain
#15
Naoki Tsuno, Akira Yukimasa, Osamu Yoshida, Shinji Suzuki, Hiromi Nakai, Tomoyuki Ogawa, Motohiro Fujiu, Kenji Takaya, Azusa Nozu, Hiroki Yamaguchi, Hidetoshi Matsuda, Satoko Funaki, Natsue Yamanada, Miki Tanimura, Daiki Nagamatsu, Toshiyuki Asaki, Narumi Horita, Miyuki Yamamoto, Mikie Hinata, Masahiko Soga, Masayuki Imai, Yasuhide Morioka, Toshiyuki Kanemasa, Gaku Sakaguchi, Yasuyoshi Iso
A novel series of (6-aminopyridin-3-yl)(4-(pyridin-2-yl)piperazin-1-yl) methanone derivatives were identified as selective transient receptor potential vanilloid 4 (TRPV4) channel antagonist and showed analgesic effect in Freund's Complete Adjuvant (FCA) induced mechanical hyperalgesia model in guinea pig and rat. Modification of right part based on the compound 16d which was disclosed in our previous communication led to the identification of compound 26i as a flagship compound. In this paper, we described the details about design, synthesis and structure-activity relationship (SAR) analysis at right and left part of these derivatives (Fig...
March 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28283888/kinin-receptors-sensitize-trpv4-channel-and-induce-mechanical-hyperalgesia-relevance-to-paclitaxel-induced-peripheral-neuropathy-in-mice
#16
Robson Costa, Maíra A Bicca, Marianne N Manjavachi, Gabriela C Segat, Fabiana Chaves Dias, Elizabeth S Fernandes, João B Calixto
Kinin B1 (B1R) and B2 receptors (B2R) and the transient receptor potential vanilloid 4 (TRPV4) channel are known to play a critical role in the peripheral neuropathy induced by paclitaxel (PTX) in rodents. However, the downstream pathways activated by kinin receptors as well as the sensitizers of the TRPV4 channel involved in this process remain unknown. Herein, we investigated whether kinins sensitize TRPV4 channels in order to maintain PTX-induced peripheral neuropathy in mice. The mechanical hyperalgesia induced by bradykinin (BK, a B2R agonist) or des-Arg(9)-BK (DABK, a B1R agonist) was inhibited by the selective TRPV4 antagonist HC-067047...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28274924/dynamic-coupling-between-trpv4-and-ca-activated-sk1-3-and-ik1-k-channels-plays-a-critical-role-in-regulating-the-k-secretory-bk-channel-in-collecting-duct-cells
#17
Yue Li, Hongxiang Hu, Jin-Bin Tian, Michael X Zhu, Roger G O'Neil
The large conductance Ca2+-activated K+ channel, BK (KCNMA1), is expressed along the connecting tubule (CNT) and cortical collecting duct (CCD) where it underlies flow- and Ca2+-dependent K+ secretion. Its activity is partially under the control of the mechanosensitive TRPV4 Ca2+-permeable channel. Recently we identified three small/intermediate conductance Ca2+-activated K+ channels, SK1 (KCNN1) and SK3 (KCNN3), and IK1 (KCNN4), with notably high Ca2+-binding affinities, that are expressed in CNT/CCD and may be regulated by TRPV4-mediated Ca2+ influx...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28274876/hypotonic-stress-promotes-atp-release-reactive-oxygen-species-production-and-cell-proliferation-via-trpv4-activation-in-rheumatoid-arthritis-rat-synovial-fibroblasts
#18
Fen Hu, Zhenhai Hui, Wei Wei, Jianyu Yang, Ziyuan Chen, Bu Guo, Fulin Xing, Xinzheng Zhang, Leiting Pan, Jingjun Xu
Rheumatoid arthritis (RA) is a chronic and systemic autoimmune-disease with complex and unclear etiology. Hypotonicity of synovial fluid is a typical characteristic of RA, which may play pivotal roles in RA pathogenesis. In this work, we studied the responses of RA synovial fibroblasts to hypotonic stress in vitro and further explored the underlying mechanisms. Data showed that hyposmotic solutions significantly triggered increases in cytosolic calcium concentration ([Ca(2+)]c) of synoviocytes. Subsequently, it caused rapid release of ATP, as well as remarkable production of intracellular reactive oxygen species (ROS)...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28249987/trpv4-ion-channel-is-a-novel-regulator-of-dermal-myofibroblast-differentiation
#19
Shweta Sharma, Rishov Goswami, Michael Merth, Jonathan Cohen, Kai Y Lei, David X Zhang, Shaik O Rahaman
Scleroderma is a multisystem fibroproliferative disease with no effective medical treatment. Myofibroblasts are critical to the fibrogenic tissue repair process in the skin and many internal organs. Emerging data support a role for both matrix stiffness, and transforming growth factor β1 (TGFβ1), in myofibroblast differentiation. Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel activated by both mechanical and biochemical stimuli. The objective of this study was to determine the role of TRPV4 in TGFβ1- and matrix stiffness-induced differentiation of dermal fibroblasts...
March 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28244642/carbenoxolone-inhibits-trpv4-channel-initiated-oxidative-urothelial-injury-and-ameliorates-cyclophosphamide-induced-bladder-dysfunction
#20
Xiling Zhang, Shan Gao, Masayoshi Tanaka, Zhen Zhang, Yanru Huang, Takahiko Mitsui, Manabu Kamiyama, Schuichi Koizumi, Jianglin Fan, Masayuki Takeda, Jian Yao
Carbenoxolone (CBX) is a clinically prescribed drug for the treatment of digestive ulcer and inflammation. It is also a widely used pharmacological inhibitor of several channels in basic research. Given that the overactivity of several channels, including those inhibitable by CBX, underlies bladder dysfunction, we tested the potential therapeutic application and mechanism of CBX in the treatment of voiding dysfunction. In a mouse model of cystitis induced by cyclophosphamide (CYP), CBX administration prevented the CYP-elicited increase in bladder weight, oedema, haemorrhage, and urothelial injury...
February 28, 2017: Journal of Cellular and Molecular Medicine
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